Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice.

Abstract

The analgesic and anti-hyperalgesic effects of cannabinoid- and vanilloid-like compounds, plus the fatty acid amide hydrolase (FAAH) inhibitor Cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597), and acetaminophen, were evaluated in the phenyl-p-quinone (PPQ) pain model, using different routes of administration in combination with opioid and cannabinoid receptor antagonists. All the compounds tested produced analgesic effects. Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide) were active by three routes of administration: i.p., s.c. and, p.o. Delta(9)-THC produced ED(50)s of 2.2 mg/kg (0.3-15.6) i.p., 9 mg/kg (4.3-18.9) s.c., and 6.4 mg/kg (5.5-7.6) p.o. Similarly, (R)-methanandamide yielded ED(50)s of 2.9 mg/kg (1-8) i.p., 11 mg/kg (7-17) s.c., and 11 mg/kg (0.9-134) p.o. N-vanillyl-arachidonyl-amide (arvanil) was active by two routes, producing ED(50)s of 4.7 mg/kg (3.0-7.4) s.c. and 0.06 mg/kg (0.02-0.2) i.p. Palmitoylethanolamide, URB597, and acetaminophen were active i.p., resulting in ED(50)s of 3.7 mg/kg (3.2-4.2), 22.9 mg/kg (11.1-47.2), and 160 mg/kg (63-405), respectively. None of the cannabinoid or opioid receptor antagonists tested blocked the compounds evaluated, with two exceptions: the antinociceptive effects of Delta(9)-THC and URB597 were completely blocked by SR141716A, a cannabinoid CB(1) receptor antagonist. Western immunoassays performed using three opioid receptor antibodies, a cannabinoid CB(1) receptor antibody and a transient receptor potential vanilloid type 1(TRPV(1)) receptor antibody, yielded no change in receptor protein levels after short-term arvanil, (R)-methanandamide or Delta(9)-THC administration. These data suggest that all the compounds tested, except Delta(9)-THC and URB597, produced analgesia via a non-cannabinoid CB(1), non-cannabinoid CB(2) pain pathway not yet identified.

• Authors: Victoria L Haller, Diana L Cichewicz, Sandra P Welch
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 546 Issue 1-3 Pg. 60-8 (Sep 28 2006) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16919265 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amides
• Analgesics
• Arachidonic Acids
• Benzamides
• Benzoquinones
• Camphanes
• Carbamates
• Endocannabinoids
• Ethanolamines
• Narcotic Antagonists
• Palmitic Acids
• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• Receptors, Opioid
• SR 144528
• TRPV Cation Channels
• TRPV1 receptor
• arvanil
• cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
• methanandamide
• Acetaminophen
• phenylbenzoquinone
• palmidrol
• Dronabinol
• Rimonabant
• Capsaicin

Topics

• Acetaminophen (pharmacology)
• Amides
• Analgesics (pharmacology, therapeutic use)
• Animals
• Arachidonic Acids (pharmacology)
• Benzamides (pharmacology)
• Benzoquinones
• Camphanes (pharmacology)
• Capsaicin (analogs & derivatives, pharmacology)
• Carbamates (pharmacology)
• Dose-Response Relationship, Drug
• Dronabinol (pharmacology)
• Endocannabinoids
• Ethanolamines
• Hyperalgesia (metabolism, prevention & control)
• Male
• Mesencephalon (chemistry, drug effects, metabolism)
• Mice
• Mice, Inbred ICR
• Narcotic Antagonists (pharmacology)
• Pain (chemically induced, metabolism, prevention & control)
• Palmitic Acids (pharmacology)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Receptor, Cannabinoid, CB1 (analysis, drug effects, metabolism)
• Receptor, Cannabinoid, CB2 (drug effects, metabolism)
• Receptors, Opioid (analysis, drug effects, metabolism)
• Rimonabant
• Spinal Cord (chemistry, drug effects, metabolism)
• TRPV Cation Channels (analysis, drug effects, metabolism)